Get into the groove! Targeting antigens to MHC class II.

The activation of MHC class II-restricted helper T cells is paramount to adaptive immune responses. Vaccine development could therefore benefit from improved ways of targeting antigens into MHC class II molecules. In recent years, the natural pathways of MHC class II antigen presentation have been exploited to achieve this goal. First, antigenic proteins and peptides have been modified to facilitate receptor-mediated uptake by professional antigen-presenting cells. Second, DNA constructs containing specific targeting sequences have been used to direct endogenously synthesized antigens to the MHC class II compartments. Both strategies proved to be highly effective. We review these data and describe how this knowledge is currently applied to the design of vaccines that activate helper T cells in vivo.